Part 1 - Dose-Ranging. Part 1 will evaluate the (1) safety and tolerability and (2) efficacy (antiretroviral activity) of 4 doses of doravirine (MK-1439) compared with efavirenz, when each is given in combination with TRUVADA® for at least 24 weeks in approximately 200 participants. A single dose of doravirine will be selected for further study after all participants complete the Week 24 visit in Part 1. Participants receiving any dose of doravirine in Part 1 will be switched to the selected doravirine dose and continue in the study for up to 96 weeks.

Part 2 - Selected Dose. Part 2 will be initiated after the doravirine dose has been selected as indicated above for Part 1. Approximately 120 additional participants will be randomized in 1:1 ratio to the selected dose of doravirine or efavirenz, each in combination with TRUVADA® for 96 weeks of blinded treatment. Part 2 will evaluate the safety of the selected dose compared with efavirenz, particularly with regard to central nervous system adverse events (CNS events).

The hypothesis tested in this study is that MK-1439 at the final dose selected is superior to efavirenz, each given in combination with TRUVADA®, as measured by the proportion of participants with CNS events by Week 8. If superiority is established at Week 8, the same hypothesis will be tested for Week 24.

doravirine 25 mg + TRUVADA® Participants in this arm will receive doravirine 25 mg in Part 1 and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz.

Drug: Doravirine

Part 1: doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching doravirine orally every morning with or without food for at least 24 weeks When the doravirine selected dose is determined after all participants reach Week 24, participants on other doses of doravirine will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of doravirine (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching doravirine orally every morning with or without food for 96 weeks

Doravirine 50 mg + TRUVADA® Participants in this arm will receive doravirine 50 mg in Part 1 and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz.

Drug: Doravirine

Part 1: doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching doravirine orally every morning with or without food for at least 24 weeks When the doravirine selected dose is determined after all participants reach Week 24, participants on other doses of doravirine will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of doravirine (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching doravirine orally every morning with or without food for 96 weeks

Doravirine 100 mg + TRUVADA® Participants in this arm will receive doravirine 100 mg in Part 1 and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz.

Drug: Doravirine

Part 1: doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching doravirine orally every morning with or without food for at least 24 weeks When the doravirine selected dose is determined after all participants reach Week 24, participants on other doses of doravirine will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of doravirine (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching doravirine orally every morning with or without food for 96 weeks

Doravirine 200 mg + TRUVADA® Participants in this arm will receive doravirine 200 mg in Part 1 and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part 2. These participants also receive placebo that matches efavirenz.

Drug: Doravirine

Part 1: doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) tablet or placebo matching doravirine orally every morning with or without food for at least 24 weeks When the doravirine selected dose is determined after all participants reach Week 24, participants on other doses of doravirine will be switched to the selected dose for the remainder of the 96-week study. Part 2: Selected dose of doravirine (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet or placebo matching doravirine orally every morning with or without food for 96 weeks

No signs of active pulmonary disease within 45 days before the start of study treatment

Clinically stable with no signs or symptoms of acute infection

No change in clinical status or chronic medications for at least 2 weeks before the start of study treatment

Participants of reproductive potential agree to remain abstinent in line with their preferred and usual lifestyle or use (or have their partner use) 2 acceptable methods of birth control throughout the study and for 12 weeks post study.

Participants not of reproductive potential, not sexually active, whose current partner(s) is not of reproductive potential, or whose sexual activity is exclusively homosexual are eligible without requiring the use of contraception.

Exclusion Criteria:

Males planning to impregnate or provide sperm donation for the duration of

the study plus an additional 12 weeks. Females pregnant or breast-feeding or expecting to conceive or donate eggs for the duration of the study plus an additional 12 weeks.

Received any approved or experimental antiretroviral agents or is

anticipated to receive such medications during the study.

Use of any immunomodulators or immunosuppressive therapy within one

month before the study. Short courses of corticosteroids (e.g., for asthma exacerbation) are allowed.

Treatment for a viral infection other than HIV, such as hepatitis B, with

Participation in a study with an investigational compound/device within

one month or is anticipating to participate in such a study during this study

Contacts and Locations

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